Research is directed toward an understanding of three systems which are obligatory for hemostasis and thrombus formation: fibrinogen and its transformation into a fibrin clot, prothrombin and its conversion into thrombin, and platelets and their responses to perturbation. (1) The development of fibrin clot structure inherently involves an enzymatic conversion by thrombin fibrinogen into monomer fibrin, and a set of four association reactions, involving monomer fibrin, which lead to the random cross linked fibrin network. Our objective is to specify reactions more quantitatively and to determine the particular effects of the entire sequence produced by physiologically active agents such as certain of the fibrinogen/fibrin degradation products. (2) The final step, in the intrinsic and extrinsic systems, when thrombin is formed, involves concerted interactions of prothrombin, calcium ion, F-V, F-Xa and colloidal lipoprotein. Our objective is to specify the organization of converting loci, the molecular mechanism of conversion, and the feedback contributions by which thrombin production is controlled. (3) Platelets respond to stimuli via their metabolic activities and adhere, aggregate and release constituents active in hemostasis. Our objectives are a specification of the minimum requirements of environmental micro-and macromolecular components to maintain normal platelet plasma response and to examine these and any further requirements for expression of the full hemostatic sequence. BIBLIOGRAPHIC REFERENCE: Landis, W.J. & Waugh, D.F. (1975) Interactions of bovine fibrinogen and thrombin. Early events in the development of clot structure. Archives of Biochemistry and Biophysics, 168, 498.